Understanding the Effects of Anti-Human CD28 Superagonistic Antibodies
Author Information
Author(s): Waibler Zoe, Sender Linda Y., Merten Camilla, Hartig Roland, Kliche Stefanie, Gunzer Matthias, Reichardt Peter, Kalinke Ulrich, Schraven Burkhart
Primary Institution: Paul-Ehrlich-Institut, Langen, Germany
Hypothesis
CD28 superagonists can activate T cells without TCR engagement and may have different effects in humans compared to non-human primates.
Conclusion
The study reveals that CD28 superagonists induce a sustained calcium response in human T cells, which is linked to the production of pro-inflammatory cytokines.
Supporting Evidence
- CD28 superagonists activate T cells without TCR engagement.
- TGN1412 caused severe adverse effects in a clinical trial.
- Sustained calcium response is linked to cytokine production.
- Human T cells respond differently to CD28 superagonists compared to non-human primates.
- Both ANC28.1 and TGN1412 induce high levels of pro-inflammatory cytokines.
Takeaway
This study shows that certain antibodies can make immune cells very active without needing a second signal, but this can sometimes cause serious side effects in humans.
Methodology
The study involved in vitro experiments with human T cells stimulated by CD28 superagonists and analyzed for calcium responses and cytokine production.
Limitations
The study primarily focuses on human T cells and may not fully represent responses in other species.
Participant Demographics
Healthy human volunteers were used for T cell isolation.
Digital Object Identifier (DOI)
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